scholarly journals The ciliary GTPase Arl3 maintains tissue architecture by directing planar spindle orientation during epidermal morphogenesis

Development ◽  
2019 ◽  
Vol 146 (9) ◽  
pp. dev161885 ◽  
Author(s):  
Samip R. Bhattarai ◽  
Salma Begum ◽  
Rachel Popow ◽  
Ellen J. Ezratty
Keyword(s):  
Spindle Orientation ◽  
Tissue Architecture ◽  
Epidermal Morphogenesis

scholarly journals A transgenic toolkit for visualizing and perturbing microtubules reveals unexpected functions in the epidermis

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Andrew Muroyama ◽  
Terry Lechler
Keyword(s):  
Growth Rate ◽  
Cell Types ◽  
Specific Cell ◽  
Tissue Architecture ◽  
Physiological Functions ◽  
Epidermal Morphogenesis ◽  
Dynamics And Function ◽  
And Function ◽  
Genetic Toolkit ◽  
Epidermal Development

The physiological functions of microtubules (MTs) are poorly understood in many differentiated cell types. We developed a genetic toolkit to study MT dynamics and function in diverse cells. Using TRE-EB1-GFP mice, we found that MT dynamics are strongly suppressed in differentiated keratinocytes in two distinct steps due to alterations in both growth rate and lifetime. To understand the functions of these MT populations, we developed TRE-spastin mice to disrupt MTs in specific cell types. MT perturbation in post-mitotic keratinocytes had profound consequences on epidermal morphogenesis. We uncoupled cell-autonomous roles in cell flattening from non-cell-autonomous requirements for MTs in regulating proliferation, differentiation, and tissue architecture. This work uncovers physiological roles for MTs in epidermal development, and the tools described here will be broadly useful to study MT dynamics and functions in mammals.

scholarly journals Junctional tumor suppressors interact with 14-3-3 proteins to control planar spindle alignment

2019 ◽  
Vol 218 (6) ◽  
pp. 1824-1838 ◽  
Author(s):  
Yu-ichiro Nakajima ◽  
Zachary T. Lee ◽  
Sean A. McKinney ◽  
Selene K. Swanson ◽  
Laurence Florens ◽  
...  
Keyword(s):  
Cell Fate ◽  
Tumor Suppressors ◽  
Mitotic Spindle ◽  
Wing Disc ◽  
Spindle Orientation ◽  
Epithelial Proliferation ◽  
Tissue Architecture ◽  
Drosophila Wing ◽  
Discs Large

Proper orientation of the mitotic spindle is essential for cell fate determination, tissue morphogenesis, and homeostasis. During epithelial proliferation, planar spindle alignment ensures the maintenance of polarized tissue architecture, and aberrant spindle orientation can disrupt epithelial integrity. Nevertheless, in vivo mechanisms that restrict the mitotic spindle to the plane of the epithelium remain poorly understood. Here we show that the junction-localized tumor suppressors Scribbled (Scrib) and Discs large (Dlg) control planar spindle orientation via Mud and 14-3-3 proteins in the Drosophila wing disc epithelium. During mitosis, Scrib is required for the junctional localization of Dlg, and both affect mitotic spindle movements. Using coimmunoprecipitation and mass spectrometry, we identify 14-3-3 proteins as Dlg-interacting partners and further report that loss of 14-3-3s causes both abnormal spindle orientation and disruption of epithelial architecture as a consequence of basal cell delamination and apoptosis. Combined, these biochemical and genetic analyses indicate that 14-3-3s function together with Scrib, Dlg, and Mud during planar cell division.

Epithelial junctions maintain tissue architecture by directing planar spindle orientation

Nature ◽  
2013 ◽  
Vol 500 (7462) ◽  
pp. 359-362 ◽  
Author(s):  
Yu-ichiro Nakajima ◽  
Emily J. Meyer ◽  
Amanda Kroesen ◽  
Sean A. McKinney ◽  
Matthew C. Gibson
Keyword(s):  
Spindle Orientation ◽  
Tissue Architecture ◽  
Epithelial Junctions

scholarly journals RAS-mediated suppression of PAR3 and its effects on SCC initiation and tissue architecture occur independently of hyperplasia

2020 ◽  
Vol 133 (23) ◽  
pp. jcs249102
Author(s):  
Ji Ling ◽  
Maria Sckaff ◽  
Manisha Tiwari ◽  
Yifang Chen ◽  
Jingting Li ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Division ◽  
Mapk Pathway ◽  
Temporal Analysis ◽  
Current Evidence ◽  
Spindle Orientation ◽  
Tissue Architecture ◽  
Spatial Cues ◽  
Human Squamous Cell Carcinoma ◽  
E Cadherin

ABSTRACTProper epithelial development and homeostasis depends on strict control of oriented cell division. Current evidence shows that this process is regulated by intrinsic polarity factors and external spatial cues. Owing to the lack of an appropriate model system that can recapitulate the architecture of the skin, deregulation of spindle orientation in human epithelial carcinoma has never been investigated. Here, using an inducible model of human squamous cell carcinoma (SCC), we demonstrate that RAS-dependent suppression of PAR3 (encoded by PARD3) accelerates epithelial disorganization during early tumorigenesis. Diminished PAR3 led to loss of E-cadherin-mediated cell adhesion, which in turn contributed to misoriented cell division. Pharmacological inhibition of the MAPK pathway downstream of RAS activation reversed the defects in PAR3 expression, E-cadherin-mediated cell adhesion and mitotic spindle orientation. Thus, temporal analysis of human neoplasia provides a powerful approach to study cellular and molecular transformations during early oncogenesis, which allowed identification of PAR3 as a critical regulator of tissue architecture during initial human SCC development.

scholarly journals Epithelial geometry regulates spindle orientation and progenitor fate during formation of the mammalian epidermis

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Kimberly Box ◽  
Bradley W Joyce ◽  
Danelle Devenport
Keyword(s):  
Cell Fate ◽  
Planar Cell Polarity ◽  
Time Lapse ◽  
Mouse Embryos ◽  
Spindle Orientation ◽  
Basal Cells ◽  
Tissue Architecture ◽  
Cell Geometry ◽  
Oriented Cell Division ◽  
Time Lapse Imaging

The control of cell fate through oriented cell division is imperative for proper organ development. Basal epidermal progenitor cells divide parallel or perpendicular to the basement membrane to self-renew or produce differentiated stratified layers, but the mechanisms regulating the choice between division orientations are unknown. Using time-lapse imaging to follow divisions and fates of basal progenitors, we find that mouse embryos defective for the planar cell polarity (PCP) gene, Vangl2, exhibit increased perpendicular divisions and hyperthickened epidermis. Surprisingly, this is not due to defective Vangl2 function in the epidermis, but to changes in cell geometry and packing that arise from the open neural tube characteristic of PCP mutants. Through regional variations in epidermal deformation and physical manipulations, we show that local tissue architecture, rather than cortical PCP cues, regulates the decision between symmetric and stratifying divisions, allowing flexibility for basal cells to adapt to the needs of the developing tissue.

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